Method and apparatus for directing therapeutic nanoparticle-labeled cells to selected locations within the body and/or for retaining therapeutic nanoparticle-labeled cells at selected locations within the body

ABSTRACT

A method for directing therapeutic nanoparticle-labeled cells to selected locations within the body and/or for retaining therapeutic nanoparticle-labeled cells at selected locations within the body, the method comprising: providing an article comprising a body of material configured to be secured about the body of a patient and having a plurality of pockets thereon, wherein each pocket is sized to receive and retain one or more magnets therein; injecting therapeutic USPIO nanoparticle-containing cells into a target therapy site; securing the article to the body of the patient; and inserting at least one magnet into at least one pocket so as to provide a desired magnetic field for further directing therapeutic nanoparticle-labelled cells to a target therapy site and/or for retaining therapeutic nanoparticle-labeled cells at the target therapy site.

REFERENCE TO PENDING PRIOR PATENT APPLICATION

This patent application claims benefit of pending prior U.S. ProvisionalPat. Application Serial No. 62/152,546, filed Apr. 24, 2015 by Andrew M.Blecher for METHOD AND APPARATUS FOR DIRECTING THERAPEUTICNANOPARTICLE-LABELED CELLS TO SELECTED LOCATIONS WITHIN THE BODY AND/ORFOR RETAINING THERAPEUTIC NANOPARTICLE-LABELED CELLS AT SELECTEDLOCATIONS WITHIN THE BODY (Attorney’s Docket No. BLECHER-2 PROV), whichpatent application is hereby incorporated herein by reference.

FIELD OF THE INVENTION

This invention relates to methods and apparatus for directingtherapeutic cells to selected locations within the body and/or forretaining therapeutic cells at selected locations within the body, andmore particularly to methods and apparatus for directing therapeuticnanoparticle-labeled cells to selected locations within the body and/orfor retaining therapeutic nanoparticle-labeled cells at selectedlocations within the body.

BACKGROUND OF THE INVENTION

Companies are now developing ultra-small, superparamagnetic iron oxide(USPIO) nanoparticles which have a coating that enables thenanoparticles to be readily taken up by cells without the aid oftransfection agents. Once the USPIO nanoparticles have been taken up bythe cells, the USPIO nanoparticles are confined to vacuoles within thecells. The USPIO nanoparticles then effectively “label” the cells. Suchlabeling does not adversely affect the cells - the cells remain healthyand retain normal function after USPIO nanoparticle labeling.

USPIO nanoparticles can be used as a contrast agent for enhancedmagnetic resonance imaging (MRI). In addition, labeled cells (i.e.,cells labeled with USPIO nanoparticles) can be created in the laboratoryand then introduced into the body for enhanced MRI. Among other things,labeled cells can be created, frozen and stored; after thawing, thecells remain viable and can be introduced into the body while retainingtheir USPIO nanoparticle labels.

This system has been successfully tested using a wide range of differentcell types.

It has been suggested that it is possible to use external magneticfields to “steer” therapeutic USPIO nanoparticle-containing cells towarda desired site in the body in order to provide therapy to, and/or toenhance imaging of, that site. Thus, the labeled, USPIOnanoparticle-containing cells may be injected into the body and thenmagnetically steered toward the therapy site.

Unfortunately, such magnetic “steering” of therapeutic USPIOnanoparticle-containing cells is difficult to achieve in practice giventhe tools currently available and, even where the therapeutic USPIOnanoparticle-containing cells are successfully steered toward thetherapy site, it can be difficult to retain the therapeutic USPIOnanoparticle-containing cells at the site, particularly over extendedperiods of time and/or where the patient is mobile.

SUMMARY OF THE INVENTION

In accordance with the present invention, there is provided a novelmethod and apparatus for directing therapeutic USPIOnanoparticle-labeled cells to selected locations within the body and/orfor retaining therapeutic USPIO nanoparticle-labeled cells at selectedlocations within the body.

More particularly, and as will hereinafter be discussed in furtherdetail, this is achieved by providing an article (e.g., a sleeve, awrap, a covering, a brace, etc.) for disposition about an area of theanatomy (e.g., a knee, shoulder, ankle, hip, elbow, hand, spine, thigh,etc.), wherein the article provides a plurality of pockets orcompartments or enclosures for receiving magnets which can be used tocreate a localized magnetic field in order to steer therapeutic USPIOnanoparticle-labeled cells to a therapy site within the body and/or toretain the therapeutic USPIO nanoparticle-labeled cells at that locationover extended periods of time and/or while the patient is mobile. Forthe purposes of the present invention, the terms “pockets” and“compartments” and “enclosures” are intended to have the same meaningand may be used interchangeably.

In one preferred form of the invention, there is provided a method fordirecting therapeutic nanoparticle-labeled cells to selected locationswithin the body and/or for retaining therapeutic nanoparticle-labeledcells at selected locations within the body, the method comprising:

-   providing an article comprising a body of material configured to be    secured about the body of a patient and having a plurality of    pockets thereon, wherein each pocket is sized to receive and retain    one or more magnets therein;-   injecting therapeutic USPIO nanoparticle-containing cells into a    target therapy site;-   securing the article to the body of the patient; and-   inserting at least one magnet into at least one pocket so as to    provide a desired magnetic field for further directing therapeutic    nanoparticle-labelled cells to a target therapy site and/or for    retaining therapeutic nanoparticle-labeled cells at the target    therapy site.

In another preferred form of the invention, there is provided apparatusfor directing therapeutic nanoparticle-labeled cells to selectedlocations within the body and/or for retaining therapeuticnanoparticle-labeled cells at selected locations within the body, theapparatus comprising an article comprising a body of material configuredto be secured about the body of a patient, and a plurality of pocketsthereon, wherein each pocket is sized to receive and retain one or moremagnets therein.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

These and other objects and features of the present invention will bemore fully disclosed or rendered obvious by the following detaileddescription of the preferred embodiments of the invention, which is tobe considered together with the accompanying drawings wherein likenumbers refer to like parts, and further wherein:

FIGS. 1-3 are schematic views showing a novel article for dispositionabout the knee of a patient, wherein the novel article is configured toreceive magnets which can be used to create a localized magnetic fieldin order to steer therapeutic USPIO nanoparticle-labeled cells to atherapy site within the body and/or to retain the therapeutic USPIOnanoparticle-labeled cells at that location over extended periods oftime and/or while the patient is mobile;

FIG. 4 is a schematic view showing a novel article for disposition aboutthe shoulder of a patient, wherein the novel article is configured toreceive magnets which can be used to create a localized magnetic fieldin order to steer therapeutic USPIO nanoparticle-labeled cells to atherapy site within the body and/or to retain the therapeutic USPIOnanoparticle-labeled cells at that location over extended periods oftime and/or while the patient is mobile;

FIG. 5 is a schematic view showing a novel article for disposition aboutthe ankle of a patient, wherein the novel article is configured toreceive magnets which can be used to create a localized magnetic fieldin order to steer therapeutic USPIO nanoparticle-labeled cells to atherapy site within the body and/or to retain the therapeutic USPIOnanoparticle-labeled cells at that location over extended periods oftime and/or while the patient is mobile; and

FIGS. 6-10 are schematic views showing a novel article for dispositionabout the calf of a patient, wherein the novel article is configured toreceive magnets which can be used to create a localized magnetic fieldin order to steer therapeutic USPIO nanoparticle-labeled cells to atherapy site within the body and/or to retain the therapeutic USPIOnanoparticle-labeled cells at that location over extended periods oftime and/or while the patient is mobile.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In accordance with the present invention, there is provided a novelmethod and apparatus for directing therapeutic USPIOnanoparticle-labeled cells to selected locations within the body and/orfor retaining therapeutic USPIO nanoparticle-labeled cells at selectedlocations within the body.

More particularly, and as will hereinafter be discussed in furtherdetail, this is achieved by providing an article (e.g., a sleeve, awrap, a covering, a brace, etc.) for disposition about an area of thebody (e.g., a knee, shoulder, ankle, hip, elbow, hand, spine, thigh,etc.), wherein the article provides a plurality of pockets orcompartments or enclosures for receiving magnets which can be used tocreate a localized magnetic field in order to steer therapeutic USPIOnanoparticle-labeled cells to a therapy site within the body and/or toretain the therapeutic USPIO nanoparticle-labeled cells at that locationover extended periods of time and/or while the patient is mobile. Again,for the purposes of the present invention, the terms “pockets” and“compartments” and “enclosures” are intended to have the same meaningand may be used interchangeably.

By way of example but not limitation, in the field of orthopedics, it iscommon to provide injectable therapies (e.g., viscosupplementation orregenerative therapies such as platelet rich plasma or stem celltreatment) to selected sites in the body (e.g., the knee, shoulder,ankle, hip, elbow, hand, spine, thigh, etc.). By way of further examplebut not limitation, in the non-orthopedic field, it is common to provideinjectable therapeutic cells for the treatment of tumors, infections,vascular lesions, etc. These therapies provide their therapeuticbenefits via the interaction of the injected cells with the cells of thetarget tissue. However, when the injectable cells fail to reach thetarget tissue and/or where the injectable cells migrate away from thesite of the target tissue (i.e., the therapy site), the injectable cellsare no longer able to provide their benefits. Increasing the accuracywith which the injectable cells are delivered to the target site, and/orincreasing the “dwell time” that the injectable cells remain at thetarget site, can improve their therapeutic effects and improve patientoutcomes.

Therefore, in accordance with the present invention, the injectabletherapeutic cells are labeled with USPIO nanoparticles, and then theUSPIO nanoparticle-containing cells are injected into the target therapysite. The USPIO nanoparticle-containing cells may then be furthertargeted toward the target tissue, and/or better maintained at thelocation of the target tissue, via a localized, tailored magnetic field.This approach has the potential to improve the clinical outcomes oforthopedic and non-orthopedic therapies that are provided to millions ofpeople worldwide.

In accordance with the present invention, there is provided variousarticles (e.g., sleeves, wraps, coverings, braces, etc.) that can beplaced around various parts of the body such as the knee, shoulder,ankle, hip, elbow, hand, spine, thigh, etc. These articles areconfigured to receive and hold magnets therein, with the magnets beingarranged so as to create the desired magnetic field around the anatomywhich is to receive the therapeutic USPIO nanoparticle-labeled cells.

More specifically, the articles (e.g., sleeves, wraps, coverings,braces, etc.) are provided with pockets or compartments or enclosuresfor receiving the magnets, with the pockets or compartments orenclosures being disposed about the therapeutic site so that appropriatemagnets may be positioned in appropriate ones of the pockets orcompartments or enclosures so as to create the desired magnetic fieldabout the therapy site, whereby to further direct the USPIOnanoparticle-containing cells to the target tissue and/or to maintainthe USPIO nanoparticle-containing cells at the target tissue. It will beappreciated that the magnets may be of different strengths or sizes, andmay be deployed at different locations on the article, so as to generatethe desired magnetic field about the anatomy (i.e., about the therapysite).

By way of example but not limitation, some of the pockets orcompartments or enclosures of the article (e.g., sleeves, wraps,coverings, braces, etc.) may have one or more magnets therein and othersof the pockets or compartments or enclosures may have no magnetstherein. Where a given pocket or compartment or enclosure has one ormore magnets therein, the magnets may all be of one given strength(and/or size), or the magnets may all be of another given strength(and/or size), or the magnets may be a mix of different strengths(and/or sizes).

Thus, the magnetic fields created by placing appropriate magnets inappropriate ones of the pockets or compartments or enclosures of thearticle (e.g., sleeve, wrap, coverings, brace, etc.) work with theinjected therapeutic USPIO nanoparticle-containing cells so as tofurther direct the therapeutic USPIO nanoparticle-containing cells tothe target tissue and/or to maintain the therapeutic USPIOnanoparticle-containing cells at the target tissue, whereby to increasetheir tissue residency time and therefore improve their therapeuticbenefits.

See, for example, FIGS. 1-3 , which show an exemplary article 5 (e.g.,sleeve, wrap, covering, brace, etc.) for the knee. Article 5 generallycomprises a body of material 10 configured to be secured about the kneeof the patient, e.g., article 5 may comprise a compression sleeve formaking a gripping fit about the knee of the patient. Alternatively,article 5 may comprise a wrap for securement about the knee of thepatient. Or article 5 may comprise a brace for securement about the kneeof a patient. Or article 5 may comprise another article of the sort wellknown to those skilled in the art. Note that article 5 may be functionalin nature (e.g., to provide a bandage covering, anatomical support, heatretention, etc.) or article 5 may simply serve to support magnets at theappropriate locations about the patient’s anatomy.

Article 5 generally comprises a plurality of pockets (or compartments orenclosures) 15 which are each sized to receive and retain one or moremagnets 20 therein. By way of example but not limitation, pockets 15 maybe generally rectangular, and closed on three sides and open (oropenable) on one side, so as to allow one or more magnets to be insertedinto (or removed from) a given pocket 15. A closure (e.g., a Velcrofastener) may be provided on the open (or openable) side to allow thepocket to be closed. Pockets 15 may also comprise other (e.g.,non-rectangular) shapes if desired. It should be appreciate that pockets15 may all be of the same shape or pockets 15 may comprise a variety ofshapes.

In one preferred form of the invention, pockets 15 are distributed aboutsubstantially the entire outer surface of the article and pockets 15 aredistributed about article 5 with a regular pattern so as to allow one ormore magnets to be disposed at substantially any location on article 5.In another preferred form of the invention, pockets 15 may bedistributed at only selected locations about article 5 so as to allowone or more magnets 20 to be disposed at selected locations on article5.

It should be appreciated that article 5 is configured to be secured tothe anatomy of the patient so that the magnets 20 carried by article 5steer therapeutic USPIO nanoparticle-labeled cells to a desired therapysite within the body, and/or so that the magnets 20 carried by article 5act to retain the therapeutic USPIO nanoparticle-labeled cells at thatlocation within the body over extended periods of time and/or while thepatient is mobile.

FIG. 4 shows an exemplary article 5 (e.g., a sleeve, wrap, covering,brace, etc.) adapted to be worn on the shoulder of a patient.

FIG. 5 shows an exemplary article (e.g., a sleeve, wrap, covering,brace, etc.) adapted to be worn on the ankle of a patient.

FIGS. 6-10 show an exemplary article (e.g., a sleeve, wrap, covering,brace, etc.) adapted to be worn on the calf of a patient. Note howmagnets 20 are positioned with different dispositions in FIGS. 6-10 ,illustrating how the present invention provides the opportunity toposition appropriate magnets 20 at appropriate locations about the calfof the patient.

It should be appreciated that, in addition to customizing the magneticfield provided about the target tissue by varying the locations ofmagnets 20 on article 5, it is also possible to tailor the magneticfield by controlling the orientation of magnets 20 provided on article5. By way of example but not limitation, magnets 20 may be arrangedrelative to one another such that their individual magnetic fields forma composite magnetic field having the desired properties. In one form ofthe invention, magnets 20 may be disposed in pockets 15 such that theycomprise a Halbach array, thereby generating an augmented magnetic fieldon one side of the magnet array while canceling the magnetic field tozero (or near zero) on the other side of the magnet array. In anotherform of the invention, magnets 20 may be disposed in pockets 15 suchthat they comprise a Halbach cylinder, thereby generating an augmentedmagnetic field within the cylinder while canceling the magnetic field tozero (or near zero) outside the cylinder.

Additionally, it should be appreciated that the ultra-smallsuperparamagnetic iron oxide (USPIO) nanoparticles (and hence, the USPIOnanoparticle-containing cells) can be visualized using imaging such asMRI (e.g., with the USPIO nanoparticles acting as a contrast agent,image enhancer, etc.). Therefore, after the USPIOnanoparticle-containing cells have been injected into the body, theirlocations can be visualized and potentially tracked via MRI.Significantly, the magnetic fields provided by novel article 5 (e.g.,sleeve, wrap, covering, brace, etc.) can be customized “on the fly” byobserving (by MRI imaging) the location of the USPIOnanoparticle-containing cells, e.g., by adding (or removing) magnets 20to (or from) appropriate pockets 15 (or other enclosures) so as totailor the magnetic field and thereby help maximize the location of theinjected therapies based on the information obtained through imaging,i.e., to further direct the USPIO nanoparticle-containing cells to thetarget tissue and/or to maintain the USPIO nanoparticle-containing cellsat the target tissue. Article 5 (e.g., sleeve, wrap, covering, brace,etc.) is, therefore, preferably constructed so as to allow foradjustments in its associated magnetic fields in order to optimize thelocation of the injected therapies based on the information provided byimaging of the USPIO nanoparticle-containing cells in vivo.

MODIFICATIONS OF THE PREFERRED EMBODIMENTS

It should be understood that many additional changes in the details,materials, steps and arrangements of parts, which have been hereindescribed and illustrated in order to explain the nature of the presentinvention, may be made by those skilled in the art while still remainingwithin the principles and scope of the invention.

1-6. (canceled)
 7. Apparatus for directing therapeuticnanoparticle-labeled cells to selected locations within the body and/orfor retaining therapeutic nanoparticle-labeled cells at selectedlocations within the body, the apparatus comprising an articlecomprising a body of material configured to be secured about the body ofa patient, and a plurality of pockets thereon, wherein each pocket issized to receive and retain one or more magnets therein.
 8. Apparatusaccording to claim 7 wherein the at least one magnet is inserted intothe at least one pocket while MRI visualization is used to observe theposition of the therapeutic nanoparticle-labeled cells relative to thetarget therapy site.
 9. Apparatus according to claim 7 wherein the atleast one pocket is closed on three sides and open (or openable) on oneside.
 10. Apparatus according to claim 7 wherein the article comprises asleeve for making a gripping fit about the anatomy of the patient. 11.Apparatus according to claim 7 wherein the article comprises a wrap forsecurement about the anatomy of the patient.
 12. Apparatus according toclaim 7 wherein the article comprises a brace for securement about theanatomy of a patient.